The selective monoalkylation of dihydroxy aromatic compounds, for example, hydroquinone, presents problems because both hydroxy groups tend to react with the alkylating agent. Newman and Colla (Journal of Organic Chemistry, Vol. 39, pages 214 and 215 (1974)) state that the monoalkylation of hydroquinone represents a problem for which no generally satisfactory procedure has as yet been developed. Monoalkylation has been accomplished by using a large excess of hydroquinone, but this method is not efficient if yield is calculated on hydroquinone. In general, alkylation of hydroquinone via the monosodium salt and one equivalent of the alkylating agent gives poor yields of monoalkylated product. Alternatively, one can make a monoprotected hydroquinone, itself a difficult process, alkylate, and remove the protecting group. These workers found that aqueous dioxan gave good yields of monoalkylation product when alkali-stable alkylating agents are used, for example, tert-butyl bromoacetate, the tert-butyl group of which is not hydrolyzed off by alkali. Similarly N-methylpyrrolidone/water also gave a good yield of monoalkylated product using tert-butyl bromoacetate. However, when alkali-sensitive groups are present as in ethyl alphabromoisobutyrate, these solvent systems are ineffective. Only moderate yields of monoalkylation product are obtained with this alkylating agent using dimethylformamide or dimethylsulphoxide as solvents.
A paper by Moser (Journal of the American Chemical Society, Vol. 72, pages 1413-1415 (1950)) discloses that reaction of the disodium salt of hydroquinone with one equivalent of ethyl chloroacetate gave approximately 30% of monoalkylation product (7% of acid; 23% of ethyl ester).
In the United Kingdom Pat. No. 1,591,063, a dihydroxybenzene compound, particularly hydroquinone, is monoalkylated in an alcoholic solvent using two to three equivalents of a base. While the above process may result in commercially acceptable yields of the desired product, the purity of the final product is not suitable for many applications. In particular, the above process does not indicate any procedure for the removal of dialkylated reaction products. Minimizing these diether by-products is mandated when the final product needs to be substantially pure.